Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1.
Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are structurally related lipid mediators that act on distinct G-protein-coupled receptors to evoke similar responses, including Ca2+ mobilization, adenylate cyclase inhibition, and mitogen-activated protein (MAP) kinase activation. However, little is still known about the respective receptors. A recently cloned putative LPA receptor (Vzg-1/Edg-2) is similar to an orphan Gi-coupled receptor termed Edg-1. Here we show that expression of Edg-1 in Sf9 and COS-7 cells results in inhibition of adenylate cyclase and activation of MAP kinase (Gi-mediated), but not Ca2+ mobilization, in response to S1P. These responses are specific in that (i) S1P action is not mimicked by LPA, and (ii) Vzg-1/Edg-2 cannot substitute for Edg-1. Thus the Edg-1 receptor is capable of mediating a subset of the cellular responses to S1P.
Zondag
G C
GC
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Postma
F R
FR
Etten
I V
IV
Verlaan
I
I
Moolenaar
W H
WH
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D017874:Immediate-Early Proteins / Q000502:physiology*; D008246:Lysophospholipids / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D018411:Spodoptera; D014157:Transcription Factors / Q000502:physiology; D016335:Zinc Fingers
D000067956:Adenylyl Cyclase Inhibitors; D017874:Immediate-Early Proteins; D008246:Lysophospholipids; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid; D014157:Transcription Factors; C060506:sphingosine 1-phosphate; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013110:Sphingosine; D002118:Calcium